Abstract
BackgroundSaliva is increasingly promoted as an alternative diagnostic bio-sample to blood; however its role in respiratory disease requires elucidation. Our aim was to investigate whether C-reactive protein (CRP), procalcitonin (PCT) and neutrophil elastase (NE) could be measured in unstimulated whole saliva, and to explore differences between COPD patients and controls with normal lung function. We also determined the relationship between these salivary biomarkers and self-reported COPD-relevant metrics.MethodsSalivary CRP, PCT and NE levels were measured at each of 3 visits over a 14-day period alongside spirometry and a daily self-assessment dairy in 143 subjects: 20 never-smokers and 25 smokers with normal spirometry; 98 COPD patients [GOLD Stage I, 16; Stage II, 32; Stage III, 39; Stage IV, 11]. Twenty-two randomly selected subjects provided simultaneous blood samples.ResultsLevels of each salivary biomarker could distinguish between the above cohorts. Significant differences remained for salivary CRP and NE (p < 0.05) following adjustment for age, gender, sampling time, gum disease and total co-morbidities; but not for BMI except for salivary NE, which remained higher in smokers compared to non-smokers and stable COPD subjects (p < 0.001). Patients with acute COPD exacerbations had a median increase in all 3 salivary biomarkers (p < 0.001); CRP: median 5.74 ng/ml, [interquartile range (IQR) 2.86–12.25], PCT 0.38 ng/ml, [IQR 0.22–0.94], and NE 539 ng/ml, [IQR 112.25–1264]. In COPD patients, only salivary CRP and PCT levels correlated with breathing scores (r = 0.14, p < 0.02; r = 0.13, p < 0.03 respectively) and sputum features but not with activities of daily living. Salivary CRP and PCT concentrations strongly correlated with serum counterparts [r = 0.82, (95 % CI: 0.72–0.87), p < 0.001 by Spearman’s; and r = 0.53, (95 % CI: 0.33–0.69), p < 0.006 respectively]; salivary NE did not.ConclusionsCRP, PCT and NE were reliably and reproducibly measured in saliva, providing clinically-relevant information on health status in COPD; additionally NE distinguished smoking status. All 3 salivary biomarkers increased during COPD exacerbations, with CRP and PCT correlating well with patient-derived clinical metrics. These results provide the conceptual basis for further development of saliva as a viable bio-sample in COPD monitoring and exacerbation management.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-015-0219-1) contains supplementary material, which is available to authorized users.
Highlights
All 3 salivary biomarkers increased during Chronic Obstructive Pulmonary Disease (COPD) exacerbations, with C-reactive protein (CRP) and PCT correlating well with patient-derived clinical metrics
These results provide the conceptual basis for further development of saliva as a viable bio-sample in COPD monitoring and exacerbation management
Salivary CRP differed between the 3 groups (p < 0.002 by analysis of variance (ANOVA)), with significant increase in COPD compared to NS (0.89 ng/ml; 0.35 ng/ml, p < 0.001 by Mann Whitney U), but not to smokers (1.70 ng/ml; 1.07 ng/ml, p < 0.605)
Summary
Saliva is increasingly used as a non-invasive accessible bio-sample for point-of-care diagnostics instead of blood [1, 2] to inform on infection [3,4,5,6,7], drugs [8] and disease states [9,10,11,12,13,14,15,16,17,18], including airways inflammation. Serum and sputum CRP are elevated in COPD patients and healthy smokers [24, 25], with moderate inverse correlation of serum CRP to Forced Expiratory Volume in 1 s (FEV1) [26]. Neutrophil elastase (NE), mediator of airway pathogenesis [36, 37], is known to be elevated in smokers [38] and COPD patients [39], has a negative correlation with FEV1 in patients with expiratory volumes below 40 % predicted [40] and increases further during exacerbations [41]. Our aim was to investigate whether C-reactive protein (CRP), procalcitonin (PCT) and neutrophil elastase (NE) could be measured in unstimulated whole saliva, and to explore differences between COPD patients and controls with normal lung function. We determined the relationship between these salivary biomarkers and self-reported COPD-relevant metrics
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
